The purpose of this study is to determine a safe, effective, and systematic approach for the treatment of first isolation of Pseudomonas aemginosa (Pa) from young children with Cystic Fibrosis (CF). There is significant interest in investigating anti-pseudomonal therapies in very young children with the long-term goal of delaying or preventing chronic infection that contributes to irreversible lung disease. There has been minimal evaluation of the long-term clinical and microbiologic efficacy or safety of aggressive early intervention (i.e., intervention based on first isolation of Pa alone, in the absence of symptoms). While anti-pseudomonal therapy for first isolation of Pa will likely result in short-term eradication of Pa from respiratory cultures, it is not known whether it will improve clinical outcomes, be associated with unacceptable toxicities, or increase the rate of acquisition of resistant organisms. In an ongoing effort to address these issues, young children with CF ranging in age from 1 to 12 years will be enrolled at one of 60 clinical centers nationwide in an 18-month clinical trial that will include approximately 300 children. The clinical trial is designed to allow randomized controlled evaluation of early intervention with inhaled and oral antipseudomonal therapy in young patients with CF at first isolation of Pa from respiratory cultures. The clinical trial will investigate two different antimicrobial treatment regimens: (1) Culture-based antibiotic therapy, i.e., treatment based on microbiology findings of Pa positive respiratory cultures, and (2) Cycled antibiotic therapy, i.e., treatment provided systematically in quarterly cycles until the end of the 18-month study period. Inhaled tobramycin and oral ciprofloxacin have bean selected as first choice antimicrobials for this trial, based on a consensus conference at which therapies were selected and ranked based on the amount of evidence and of safety data available. The primary outcome of the clinical trial is the proportion of recurrent Pa positive cultures during the 18-month study period, comparing participants assigned to the culture-based treatment group with participants assigned to the cycled treatment group. Another key clinical outcome measure will evaluate the time to occurrence of a pulmonary exacerbation. The secondary outcomes will evaluate the effect of antibiotic therapy on safety (adverse events profile with particular reference to musculo-skeletal symptoms, renal function as measured by serum creatinine, hearing acuity, liver function tests, and complete blood count); clinical variables (occurrence of hospitalization during 18 months, proportion of patients with pulmonary exacerbations, linear growth, weight gain, FEV1, and total inpatient days); microbiology findings (presence and pattern of mucoid Pa isolates identified by colony morphology, changes in MICs of Pa isolates from oropharyngeal cultures, and changes in the genotype of Pa isolates from baseline to the end of the study); and Pa serology (changes in and patterns of anti-pseudomonal antibody titers against Exotoxin A and other selected pseudomonas antigens). In essence, this study will provide valuable clinical and microbiologic efficacy and safety data regarding the use of antipseudomonal therapy in young children with CF, will provide important data on the effect of PA colonization on subsequent health status, and will provide information on surrogate markers of lower airway infection.